Abstract CT067: Pembrolizumab with and without sacituzumab govitecan as first-line treatment for metastatic non-small-cell lung cancer (NSCLC) with PD-L1 TPS ≥50%: phase 3 KEYNOTE-D46/EVOKE-03 study

Abstract Background: Sacituzumab govitecan is an antibody-drug conjugate comprising an anti-trophoblast cell-surface antigen 2 (Trop-2) antibody coupled to a potent payload, SN-38, via a proprietary, hydrolysable linker. In heavily pretreated patients with metastatic NSCLC, sacituzumab govitecan showed a durable antitumor response and was well tolerated with a 10-mg/kg dose regimen. Monotherapy with the anti-PD-1 monoclonal antibody pembrolizumab is a standard-of-care therapy for patients with previously untreated advanced/metastatic NSCLC with no sensitizing EGFR or ALK alterations and a PD-L1 tumor proportion score (TPS) ≥50%. KEYNOTE-D46 evaluates whether adding sacituzumab govitecan to pembrolizumab monotherapy can improve outcomes in patients with metastatic NSCLC with PD-L1 TPS ≥50%. Trial Design: In this phase 3, open-label, active comparator-controlled, randomized study, ~614 eligible adults with previously untreated metastatic NSCLC; no EGFR, ALK, or ROS1 alterations; PD-L1 TPS ≥50%; and measurable disease per RECIST version 1.1 will be randomized 1:1 to receive either pembrolizumab 200 mg Q3W for up to 35 cycles plus sacituzumab govitecan 10 mg/kg on days 1 and 8 of each Q3W cycle (no maximum treatment duration) or pembrolizumab 200 mg Q3W for up to 35 cycles. Randomization is stratified by ECOG PS (0 vs 1), histology (squamous vs nonsquamous), and geographic region (East Asia vs North America/Western Europe/Australia vs Rest of World). Treatment continues until PD, death, unacceptable toxicity, or another treatment discontinuation criterion is met, or (for pembrolizumab) completion of 35 cycles. Dual primary endpoints are PFS per RECIST version 1.1 by blinded independent central review (BICR) and OS. Secondary endpoints include ORR and duration of response per RECIST version 1.1 by BICR, safety, and patient-reported outcomes. Radiographic imaging occurs at baseline; weeks 6, 12, 18, and 24 from randomization; every 9 weeks thereafter through week 51; and then once every 12 weeks until BICR-confirmed PD or the start of new anticancer treatment, pregnancy, withdrawal of consent, or death. PD-L1 expression status is assessed at a central laboratory using PD-L1 IHC 22C3 pharmDx (Agilent, Santa Clara, CA). Health-related quality of life is assessed using validated patient-reported outcome instruments including the EORTC Quality of Life Questionnaire-Core 30 and Quality of Life Questionnaire-Lung Cancer 13. AEs are assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Enrollment started on December 9, 2022 and is currently ongoing. Citation Format: Mor Moskovitz, Isamu Okamoto, Peng Chen, Jilpa Patel, Sabeen Mekan, M. Catherine Pietanza, Yalin Zhu, Renata Eiras, Marcello Tiseo. Pembrolizumab with and without sacituzumab govitecan as first-line treatment for metastatic non-small-cell lung cancer (NSCLC) with PD-L1 TPS ≥50%: phase 3 KEYNOTE-D46/EVOKE-03 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT067.